Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org). The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.Peer reviewedPostprin

Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration

Establishing science-based driving per se blood Δ9-tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers’ performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5–3.5 h post-dose). Occasional smokers’ odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3–18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1–1.5) and 1.5 (1.3–1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2–0.6) mm at 1.5 h and 0.5 (0.2, 0.2–0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users’ performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers’ impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases

A sensitive LC-MS/MS method for the quantitation of oxycodone, noroxycodone, 6 alpha-oxycodol, 6 beta-oxycodol, oxymorphone, and noroxymorphone in human blood

The objective of this study was to develop and validate a highly sensitive method for the detection of oxycodone, noroxycodone, 6?-oxycodol, 6?-oxycodol, oxymorphone, and noroxymorphone in blood by liquid chromatography tandem mass spectrometry. The analytes were extracted from blood (0.5 mL) using Bond Elut Certify Solid Phase Extraction columns, evaporated to dryness and reconstituted before analysis was performed on an Acquity UPLC? I-class coupled to a Waters Xevo TQD. Academy Standards Board Standard Practices for Method Development in Forensic Toxicology were used for the validation of this method. The limit of quantitation for all analytes was established at 0.5 ng/mL. Calibration range for noroxymorphone, oxymorphone, 6?-oxycodol and 6?-oxycodol was 0.5?25 ng/mL and 0.5?100 ng/mL for noroxycodone and oxycodone. Precision (2.90?17.3%) and bias studies resulted in a ?15% deviation. There were no interferences observed from internal standard, matrix, or common drugs of abuse. Stability of all analytes at two concentrations at 24, 48, and 72 h in the autosampler did not exceed ?20% difference from the initial T0. Dilution integrity at a ten-fold dilution was acceptable as analyte concentrations ranged between (?18%) of the target concentration. Once validated, the method was used in a pilot dosing study of one male subject after taking a 10 mg immediate release tablet of oxycodone. Blood samples were collected at 0.25, 0.50, 0.75, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 9, and 24 h after ingestion. Oxycodone and noroxycodone both reached Tmax at 1.5 h and had Cmax values of 25.9 and 12.8 ng/mL, respectively. Oxycodone, 6?-oxycodol, and 6?-oxycodol were detectable up to 9 h, while noroxymorphone and noroxycodone were still detected at 24 h.Funding Agencies|Strategic Research Area in Forensic Sciences at University of Linkoping, Sweden [304399, 304774]</p

The Quantification of Oxycodone and Its Phase I and II Metabolites in Urine

The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3 beta-D-glucuronide (NOMG), oxymorphone-3 beta-D-glucuronide (NOMG), noroxymorphone (NOM), oxymorphone (OM), 6 alpha-oxycodol (alpha OCL), 6 beta-oxycodol (beta OCL), noroxycodone (NOC) and oxycodone (OC) in urine by liquid chromatography tandem mass spectrometry to be used in a human study. The method was validated according to the Academy Standards Board Standard Practices for Method Development in Forensic Toxicology. The method was then applied to a single-dose pilot study of a subject. Urine samples were collected from the subject after ingesting 10-mg OC as an immediate-release tablet. Additionally, urine specimens (n = 15) that had previously been confirmed positive for OC were analyzed using the validated method. The calibration range for NOMG and OMG was 0.05-10 µg/mL; for all other analytes, it was 0.015-10 µg/mL. Validation parameters such as bias, precision, carryover and dilution integrity, all met the validation criteria. After the method was validated, urine samples from the first subject in the controlled dose study were analyzed. It was observed that OC, NOC and OMG contained the highest concentrations and were present in either the 0.5 or 1 h void. NOC and OMG were detected until the 48 h collection, while OC was detectable till the 24 h collection. Time to reach maximum concentration (T-max) in the urine was achieved within 1.5 h for OC and within 3 h for NOC and OMG. Maximum concentration (C-max) in the urine for OC, NOC and OMG was 3.15, 2.0 and 1.56 µg/mg, respectively. OC concentrations in authentic urines ranged from 0.015 to 12 µg/mL. Ranges for NOMG and OMG were 0.054-9.7 µg/mL and 0.14-67 µg/mL, respectively. A comprehensive method for the quantification of NOMG, OMG, NOM, OM, alpha OCL, beta OCL, NOC and OC in urine was optimized and met the validation criteria. The concentrations of NOMG and OMG presented in this study provide the details needed in the forensic community to better comprehend OC pharmacokinetics.Funding Agencies: Strategic Research Area in Forensic Sciences at the University of Linköping, Sweden [304399, 304774]</p

Urinary Pharmacokinetics of Immediate and Controlled Release Oxycodone and its Phase I and II Metabolites Using LC-MS-MS

Oxycodone (OC) is a schedule II semisynthetic opioid in the USA that is prescribed for its analgesic effects and has a high potential for abuse. Prescriptions for OC vary based on the dosage and formulation, immediate release (IR) and controlled release (CR). Monitoring OC metabolites is beneficial for forensic casework. The limited studies that involve pharmacokinetics of the urinary excretion of OC metabolites leave a knowledge gap regarding the excretion of conjugated and minor metabolites, pharmacokinetic differences by formulation, and the impact of CYP2D6 activity on the metabolism and excretion of OC. The objectives of this study were to compare urinary excretion of phase I and II metabolites by formulation and investigate if ratio changes over time could be used to predict the time of intake. Subjects (n = 7) received a single 10 mg IR tablet of Oxycodone Actavis. A few weeks later the same subjects received a single 10 mg CR tablet of Oxycodone Actavis. During each setting, urine was collected at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48 and 72 h. Urine samples (100 mu L) were diluted with 900 mu L internal standard mixture and analyzed on an Acquity UPLC® I-class coupled to a Waters Xevo TQD using a previously validated method. The CYP2D6 phenotypes were categorized as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM). Comparisons between IR and CR were performed using two-tailed paired t-test at a significance level of P = 0.05. The metabolite ratios showed a general increase over time. Four metabolite to parent ratios were used to predict the time of intake showing that predictions were best at the early time points.Funding Agencies: Strategic Research Area in Forensic Sciences at University of Linköping, Sweden [304399, 304774]</p

Diversity, ecology and biogeography of the genus \kur{Geophagus} s.l. [Perciformes: Cichlidae] (review)

Neotropical cichlid line Geophagini [Perciformes: Cichlidae: tribus Geophagini] isoneof the largest andmost diversified groups of cichlids. Species within the group are highlymorphologicallyvariable,show different foraging and reproductive strategies and phylogenetic relationships within this group are still not clearly established. The aim of this study was togather as much biological, ecological and biogeographical information about species Geophagus sensu lato, which form major part in diversity of Geophagini, and to summarize known phylogenetic relationships withinthe group. As an alternative hypothesis to the current interpretation of the origin of diversity within the tribe I included biogeographical analysis og this group using S-DiVA (Statistical Dispersal-Vicariance Analysis)